Ubiquitin is a highly conserved eukaryotic protein that has been suggested to play a key role in interacellular protein degradation, cell cycle regulation, DNA repair, recombination, chromatin structure, stress response, programmed cell death, and the mechanism of receptor action. In all cases it appears to exert its function by being covalently attached to target proteins by an amide bond between the C-terminal glycine of ubiquitin and an alpha or epsilon amino group on the labeled protein. A large number of members of the ubiquitin-specific processing protease (UBP) family have been identified. These proteases process the primary gene products, remove ubiquitin from other protein, and dissassemble the polyubiquitin degradation signal. In addition to ubiquitin, several other eukaryotic proteins contain ubiquitin-like domains. We will purify and characterize processing proteases that act upon the interferon-induced ubiquitin cross-reacting protein and examine their mechanism and specificity. This work will test the hypothesis that ubiquitin-like proproteins are processed by isoforms of the UBP family. Whether the hypothesis is proved or not, we will have identified the processing proteases that may be involved.